Polymeric biomaterials are used in every diagnostic or therapeutic device or implant in the cardiovascular system. Nevertheless, when flowing blood is contacted with most if not all of such biomaterials, varying degrees of thrombosis and thromboembolism result. These events represent major deterrents to the development and application of new or improved heart assist devices and cardiovascular implants, especially for longer term uses. In this program project, our objectives are to develop a fundamental understanding of the cause and effect relationships between the biomaterial bulk and surface character and its propensity to cause thrombosis or thromboembolism when contacted in vivo under different, well-defined hemodynamic situations with flowing blood. We propose to do this by synthesizing new or modified polymeric biomaterials having a range of polar/apolar compositional ration and different topographies, and then characterizing their surface chemical composition and physical topography down to dimensions of 50-100 angstrom units using new state-of-the-art instrumental (e.g., electron microprobe) techniques. We propose to measure: 1) the rates of initial protein deposition and initial platelet interactions in vitro and in vivo, 2) the steady state rate of surface-induced thrombus formation (platelet and fibrinogen consumption), 3) the size, size distribution and rate of production of emboli generated by these materials both in vitro and in vivo using a laser scattering technique, 4) the effectiveness of oral or surface bound antiplatelet drugs as inhibitors of surface-induced thrombosis in vivo, and 5) the rate of endothelialization on fabric prosthetic surfaces (lining the inside of the A-V shunt). All in vivo studies will be performed with an A-V baboon shunt system since we have found it to be a particularly relevant and useful model for studying thrombotic processes in vivo.